TY - JOUR
T1 - Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma
AU - Takada, Hiroyuki
AU - Ibaragi, Soichiro
AU - Eguchi, Takanori
AU - Okui, Tatsuo
AU - Obata, Kyoichi
AU - Masui, Masanori
AU - Morisawa, Ayaka
AU - Takabatake, Kiyofumi
AU - Kawai, Hotaka
AU - Yoshioka, Norie
AU - Hassan, Nur Mohammad Monsur
AU - Shimo, Tsuyoshi
AU - Hu, Guo Fu
AU - Nagatsuka, Hitoshi
AU - Sasaki, Akira
N1 - Includes bibliographical references.
PY - 2017/8
Y1 - 2017/8
N2 - Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Fur thermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.
AB - Head and neck squamous cell carcinomas (HNSCCs) frequently invade the bones of the facial skeleton. Semaphorin 4D (Sema4D) is an axon guidance molecule produced by oligodendrocytes. Sema4D was also identified in the bone microenvironment and many cancer tissues including HNSCC. To date, however, the role of Sema4D in cancer-associated bone disease is still unknown. This is the first study to demonstrate the role of Sema4D in bone invasion of cancer. In the clinical tissue samples of bone lesion of HNSCC, Sema4D was detected at high levels, and its expression was correlated with insulin-like growth factor-I (IGF-I) expression. In vitro experiments showed that IGF-I regulates Sema4D expression and Sema4D increased proliferation, migration and invasion in HNSCC cells. Sema4D also regulated the expression of receptor activator of nuclear factor κβ ligand (RANKL) in osteoblasts, and this stimulated osteoclastgenesis. Fur thermore, knockdown of Sema4D in HNSCC cells inhibited tumor growth and decreased the number of osteoclasts in a mouse xenograft model. Taken together, IGF-I-driven production of Sema4D in HNSCCs promotes osteoclastogenesis and bone invasion.
KW - Bone invasion
KW - Head and neck squamous cell carcinoma
KW - Insulin-like growth factor-I
KW - Osteoclastogenesis
KW - Plexin-B1
KW - Semaphorin 4D
UR - http://www.scopus.com/inward/record.url?scp=85021837917&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021837917&partnerID=8YFLogxK
U2 - 10.3892/ijo.2017.4050
DO - 10.3892/ijo.2017.4050
M3 - Article
C2 - 28656278
AN - SCOPUS:85021837917
SN - 1019-6439
VL - 51
SP - 625
EP - 632
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 2
ER -
